Entera Bio Investor Presentation - August 17th 2021 - Investor Relations | Entera Bio Ltd.
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Entera Bio Investor Presentation
August 17th 2021
1Forward-Looking Statements
This presentation includes forward-looking statements that relate to future events or our future financial performance and involve
known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or
achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by
these forward-looking statements. Forward- looking statements include all statements that are not historical facts and can be
identified by words such as, but not limited to, “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “targets,” “likely,” “will,”
“would,” “could,” and similar expressions or phrases. We have based these forward-looking statements largely on our management’s
current expectations and future events and financial trends that we believe may affect our financial condition, results of operation,
business strategy and financial needs. Although the Company believes that its expectations with respect to forward-looking
statements are based upon reasonable assumptions within the bounds of its existing knowledge of its business and operations, there
can be no assurance that actual results, performance, or achievements of the Company will not differ materially from any future
results, performance, or achievements expressed or implied by such forward-looking statements. Please refer to our SEC filings for a
complete discussion of the risks associated with our business at www.sec.gov.
NASDAQ: ENTX 2Entera Bio Investment Highlights
Platform for the Oral Delivery of Injectable Biologics and Proteins
• Two programs in clinical development
• Platform has been tested successfully on 8 molecules of broad characteristics and size
• Multiple business development opportunities; collaboration with Amgen signed in Dec 2018 around anti-inflammatory
large molecule
Lead PTH program: EB613 for Osteoporosis Headed into Pivotal Phase 3
• Phase 2 study completed, met primary and key secondary endpoints; Preparing for End of Phase 2 meeting with FDA for
planned pivotal one-year Phase 3
• Potential 1st oral bone building product; final data show dose dependent and positive impact on lumbar spine BMD
• US IND granted Dec 2020; FDA Guidance allows for use of 505(b)(2) approval pathway
Next internal PTH Program: Hypoparathyroidism EB612 (Orphan Disease)
• Phase 2 PK/PD data published in JBMR (Mar 2021); data helps define final formulations & Phase 3 pathway in 2022
• Orphan Disease Designation in both US & EU for hypoparathyroidism (HypoPT)
Large Target Markets with Significant Unmet Needs
• < 5% of osteoporosis patients are treated due to injectables’ inconvenience/compliance issues; EB613 can further grow
multi-billion $ osteoporosis market
• HypoPT market >$1 billion
• Future opportunities in other biologics, where oral delivery can grow multi billion $ markets
Management Team & Board with Capital Markets and Drug Development Expertise
NASDAQ: ENTX 3Experienced Leadership Team & Board
Experienced Leadership Team & Board
Jerry Lieberman Chairman of the Board: TEVA Board, formerly
CPA AllianceBernstein, Fidelity & Citicorp
Spiros Jamas CEO, formerly of AOBiome Therapeutics,
Sc.D Tempero Pharmaceuticals, Enanta
Pharmaceuticals, and Alpha-Beta
Technology
Phillip Schwartz President of R&D formerly of Serono, Endo
MSc, PhD Pharmaceuticals
Roger Garceau Director and Chief Development Advisor
MD formerly CMO of NPS Pharma (acquired by
Shire plc for $5.2 B) - led Natpara® approval
Arthur Santora Chief Medical Officer formerly of Merck, lead
MD, PhD clinical physician for Fosamax®, FDA & NIH
Hillel Galitzer Chief Operating Officer formerly of Optivasive Inc.
MBA, PhD and Hadasit Bio-Holdings
Dana Yaacov Israel Chief Financial Officer formerly of
MBA, CPA PricewaterhouseCoopers
Ramesh Ratan US Chief Financial Officer formerly of AOBiome,
Xcellerex, Enanta, Repligen, Bristol-Myers
Steve Engen
Head of Business Development formerly of
MBA
Locust Walk, Shire, Solasia and Mundipharma
4
NASDAQ: ENTXOral Delivery of Large Molecules is Challenging
~30% of all FDA drug approvals between 2015 and 2018 were biologics (>$20 B+ annual sales);
however biologic molecules cannot be orally formulated due to low bioavailability and high
variability
Large molecules are broken down and
degraded in the GI Tract - The human Loss of activity
GI tract is uniquely designed to digest
large molecules such as proteins and
peptides
Poor absorption
Large molecules are difficult to absorb - Significant variability in
The weight, size and charge of intact drug exposure
large molecules inhibit absorption
Historically, most technologies have focused on either enhancing absorption or protecting the molecule;
Entera has developed two technologies which function in tandem to deliver known API’s
NASDAQ: ENTX 5Our Solution: Protect and Enhance Absorption of Known Products
Protection of Proteins and Peptides
Just as the human gastro-intestinal
Combination of protease inhibitors and track digests food, biological
chemical entities protect proteins and peptides molecules such as PTH are also
Customized formulations for individual digested
molecules or API’s
Microvilli
Transport of drug
Absorption Enhancement through cell
A novel molecular entity induces endocytosis
of itself and associated molecule
Transport via vesicles is specific and safe: Intestinal cell
no bacteria or other contaminants Systemic circulation
Bloodstream
Entera’s technology platform acts synergistically to transport and protect large molecules, while
preserving and leaving the API untouched, providing rapid clinical and regulatory advantages
NASDAQ: ENTX 6Highly Predictable Delivery and Reduced Variability
Oral delivery of large molecules has been plagued by variability and lack of specificity. Entera’s
technology addresses this major technical hurdle in the oral delivery of proteins
EB613 Oral PTH (1-34) Injectable PTH (1-34)
500
500
450
450
400
Concentration (pg/ml)
400
350
Concentration (pg/ml)
350
300 300
250 250
200 200
150 150
100 100
50 50
0 0
0 50 100 150 200 250 300 0 50 100 150 200 250 300
Time (Minutes)
Time (Minutes)
Dark line is the mean of the observed release profiles.
Formulation Participants Cmax (pg/ml) Tmax (min) Coefficient of Variation (%)
EB613 Oral PTH 10 235.6 ± 36 16.5 ± 1.2 48
Injectable PTH 10 184.2 ± 26 16 ± 1.8 45
NASDAQ: ENTX 7Oral formulation development: Theoretical assessment to PK study in humans
Theoretical assessment Simulation of the
of the oral delivery human PK profile of a
feasibility based on the target molecule based
Pharmacokinetic Pharmacokinetic
physicochemical on the PK data of the
parameters and study in animals injectable formulation study in humans
pharmacology of the and results of animal
target molecule PK study
Development of oral formulation of GLP2
pharmacokinetic study in rats simulation of PK in humans
GLP2 analogs p = 0.000002 90
Plasma concentraation (ng/ml)
20
are suitable for
Plasma concentration(ng/ml)
80
18 Simulated PK profile
16 Peptide T1 + SNAC-PI 70
oral delivery 14
Peptide T1 + Mannitol (control)
60
SC injection
with ENTX 50
12
10 40
platform 8
6
30
20
4
10
2
0
0 0 100 200 300 400 500 600 700
0 30 60 90 120 150 180
Time (min)
Time (min)
NASDAQ: ENTX 8Entera’s Pipeline Focuses on both Internal Development of Approved
Injectable Therapeutics, as well as External Collaborations
~90% of current blockbuster products are injectable biologics1, Entera’s platform may be applicable to 1/3 of all biologic macromolecules
Current
Next
Program Target Preclin Phase 1 Phase 2 Phase 3 Partner Class
Milestone
Sales ($)
End-of-Phase
2 Meeting
PTH Osteoporosis EB613 PTH 1-34 505b2 $7.5 B+
with FDA
H2 2021
Hypoparathyroidism Phase 2b/3
PTH EB612 PTH 1-34 BLAOsteoporosis Incidence & Health Care Burden
WHAT IS High Levels of Incidence in the US & WW 1,2
OSTEOPOROSIS?
• Osteoporosis affects 200 million people worldwide
Systemic skeletal disease • 54 million Americans have osteoporosis or low bone mass which places them at an
characterized by low increased risk for developing osteoporosis
bone mass, deterioration • One in two women and one in four men >50 years old will break a bone due to
of bone tissue and osteoporosis
increased bone fragility
and susceptibility to
fractures High Costs & Burden of Disease 1,2
Osteoporosis is costly2
• 2 million broken bones and $19 billion in related costs each year; estimated to
reach 3 million broken bones & $25 billion in costs each year by 2025
Osteoporosis is a silent and multifactorial disease1
• Many patients don’t feel sick, can’t feel the bones weakening
• Several other diseases or treatments can increase the likelihood of osteoporosis –
autoimmune or hormonal disorders, or even common drugs such as antacids or
steroids
1. National Osteoporosis Foundation. nof.org
2. International Osteoporosis Foundation. iofbonehealth.org/facts-statistics
NASDAQ: ENTX 10High Incidence, yet Greatly Underdiagnosed and Undertreated
The first oral once daily tablet will grow the market substantially
• Benefits of bone building PTH and convenience of a daily oral tablet
• Significant cost advantages to price attractively for the 95% of patients NOT treating this disease; oral tablets are a fraction of the cost of
injectables
• Patients, Physicians, Payers and Providers seeking more cost-effective solutions
Today’s $4 B+ Market: The most effective drugs for severe osteoporosis require injections
• Annual injections cost ~$20-$30K
• Forteo® (Lilly) is a daily injection with 2019 sales of ~$1.4B1
• Prolia® (Amgen) had sales of ~$2.2B in 20192
Yesterday’s $3 B Market: Bisphosphonates are anti-resorptive agents without the ability to directly
induce new bone synthesis
• Inexpensive and convenient (oral daily pills) but not so effective - many patients continue to get worse on bisphosphonates
• GI disturbances and the risk of osteonecrosis of the jaw
• The leading bisphosphonates, Fosamax® (Merck) and Reclast® (Novartis), had peak sales of $3.2B (in 2005)3 and $1.5B (in 2010)4
respectively. No new oral drugs in over a decade
Strategy - Grow Total Addressable Market (TAM) by Treating All Patients
• Multi billion $ opportunity for new patients: realizable opportunity for 10% market penetration at 25% of today’s injectable price = $20 B +
market, and potential to take share from the 50,000 patients treated with injectables
1. Lilly YE 2019 Earnings Release
2. Amgen YE 2019 Earnings Release
3. http://www.merck.com/finance/annualreport/ar2005/pdf/Merck_2005_Financial_Section.pdf Page 23
4. https://www.novartis.com/sites/www.novartis.com/files/novartis-annual-report-2010-en.pdf page 161
NASDAQ: ENTX
11Entera Competitive Advantages: Bone Building, Inexpensive Daily Oral PTH Pill
Forteo TymlosTM Prolia Evenity® Bisphosphonates Entera
Key Product Needs ** (Lilly) (Radius) (Amgen) (Amgen) (generics) EB613
Treats Osteoporosis ✔ ✔ ✔ ✔ ✔ ✔
Rebuilds Bone ✔ ✔ ✔/~ ✔ ✔
Oral Dosing ✔ ✔
No Refrigeration ✔ ✔ ✔
Self-Administered ✔ ✔ ✔ ✔
Inexpensive COGS ✔ ✔
Product Metrics ** Target
Annual WW Sales $1.4 B $175 M $2.6 B $350 M $300M
Annual Treatment
~$35K + ~$20K + $3-5K ~$21K generics Flexible
Price
% of Market ~1%EB613: Lead Program in Osteoporosis ̶ De-risked Pathway
Product Overview
• Oral formulation of syntheticProduct
PTH (1-34)&for
Regulatory Highlights
treatment of osteoporosis
• Absorption profile is similar to Forteo® by Eli Lilly
• Strong IP including issued composition patents in major markets and additional provisional patent
applications filed in US with claims specific to the treatment of osteoporosis
Clinical and Regulatory Overview
• Received IND “May Proceed” from FDA in December 2020
• 2018 & 2019 FDA guidance: 505(b)(2) pathway, and biomarker / BMD endpoints
• Phase 2 dose ranging study in Osteoporosis completed
• Study meets primary and key secondary endpoints
• Phase 3 pivotal 12-month head-to-head study vs. Forteo® to support a 505(b)(2) submission
• Clinical trial design: non-inferiority (+/- 25% margin)
• Primary endpoints: lumbar spine bone density
• Safety: hypercalcemia, hypotension, GI disturbances
NASDAQ: ENTX 13EB613 Positioned to be the first oral bone building agent for the treatment of osteoporosis • Phase 2 study met primary and key secondary endpoints • Primary efficacy endpoint: a statistically significant increase in P1NP (a bone formation marker) at 3 months was achieved • A significant dose response was observed for 0.5, 1.0, 1.5 and 2.5 mg PTH doses on P1NP, Otseocalcin and bone mineral density (BMD) • Subjects receiving the 2.5 mg dose of EB613 showed significant dose-related increases in BMD at the lumbar spine, total hip, and femoral neck at 6 months • Subjects receiving the 2.5 mg dose of EB613 for 6 months had a significant placebo adjusted increase of 3.78% in lumbar spine BMD (p
Multiple Phase 2 & Phase 3 Milestones for EB613 in Osteoporosis
Milestone Time
Phase 2 Completed Study Enrollment Nov 2020
Regulatory US IND “May Proceed” granted by FDA Dec 2020
Phase 2 Efficacy Results: Full 3-Month Biomarker Data Mar 2021
Phase 2 Efficacy Results: Full 6-month Bone Mineral Density Data Jun 2021
Phase 3 End-of-Phase 2 FDA Discussion & Phase 3 Plan H2:2021
Phase 3 Commence Patient Enrollment 2022
NASDAQ: ENTX 15High Disease Burden in HypoPT
Condition and Ca + Vitamin D
Treatment Lead to Long-Term
72% Heavy Burden of Illness Consequences Cardiovascular
Heart failure,
of patients Symptoms include weakness, muscle
blood vessel
experience 10+ cramps, headache, brain fog1,2,3 calcification3
symptoms daily1
Neurologic
Cognitive impairment,
basal ganglia
calcification1,2
Renal
78% High Economic Impact
Kidney stones,
renal failure1,3
of working patients Hospitalization and ER visits for
miss work regularly seizures and cardiac
due to symptoms abnormalities1
and many are Skeletal
Reduced
unemployed1 bone turnover1,2
~60k insured HypoPT patients in the US
Natpara® reserved for most severe patients
1. Hadker N, Egan J, Sanders J, et al. Endocr Pract. 2014.
2. Bilezikian JP, Khan A, Potts JT, et al. J Bone Miner Res. 2011.
3. Shoback D. Hypoparathyroidism. N Engl J Med. 2008. NASDAQ: ENTX 16EB612: Phase 2a Study: Published in JBMR March 2021
Multicenter, Open-label Clinical Trial in HypoPT Patients 1
Oral Calcium Intake Study Met All Primary Endpoints
ITT Analysis (N=17)
• 42% reduction (p=0.001) from baseline in median
10%
P < 0.02 P < 0.001
calcium supplement use
0% • Maintenance of median ACa levels above the
lower target level for HypoPT patients (>7.5 mg/dL)
throughout the study
% of Starting Dose
-10%
-20%
• Rapid decline of 23% (p=0.0003) in median serum
phosphate levels 2 hours following the first dose
-30%
that was maintained for the duration of the study
• Median decrease of 21% (p=0.07) in 24-hour urine
-40%
calcium excretion between the first and last
treatment days
10
11
12
13
14
15
16
7
Base Line
1
2
3
4
5
6
8
9
-50%
Week Of Visit • Improvement in quality of life (p=0.03) from
baseline to the end of the treatment period
Galitzer, et al. “Safety and Efficacy of Oral Human Parathyroid Hormone (1-34) in Hypoparathyroidism: An Open-Label Study,” JBMR, March
1 H.
2021
NASDAQ: ENTX 17Validating our Platform: Internal R&D / External Collaborations
Target collaborations and further R&D efforts where we create sustainable innovation around
validated biology
Business Development & Collaboration Opportunities
1. Pharmaceutical companies need a new oral solution. We can help collaborators stave off
biosimilars and patent expirations, OR save development projects that would otherwise be
shelved: Technology tested successfully in 8 molecules of different characteristics and sizes
2. Lead PTH Programs (EB 613 and 612): Engaging commercial partners today following Phase
2 data read-outs
3. Select Regional deals in Asia: China market is large and growing with substantial interest in
novel technologies; substantial interest in endocrine diseases in Japan
4. New Opportunities in GLP-2 and human growth hormone: New findings show oral absorption
and bioavailability in preclinical studies
Initial Validation: Amgen Dec 2018 Collaboration: $270 m total deal value, active
preclinical work underway
NASDAQ: ENTX 18Intellectual Property & Know-How
Entera has a broad family of patents filed worldwide covering both actives and key excipients of our
formulations, expiry dates starting in 2028 to 2035
• The underlying technology patents for oral delivery of large molecules/
proteins gives basic protection to all formulations utilizing this technology
• Patents related to specific formulations for the treatment of specific
diseases adds a second level and allows for patent life extension
• Patents related to key improvements and understanding of the principles
for correct use of technology represent a third level of protection and
may be the most significant barrier to entry
• Entera controls certain critical raw materials and excipients, along with
methods and validation packages for regulatory submissions
NASDAQ: ENTX 19Leading Oral Delivery Technology Platform:
Two oral PTH programs: one headed into Phase 3 (EB 613 for osteoporosis) and
one at Phase 2 (EB 612 for HypoPT)
Announcing new programs in 2021
Milestones:
EB 613 – Phase 2 Study Met Primary and Key Secondary Endpoints
EB 613 – Present Phase 2 results at Medical Conferences in H2:21
Entera Bio EB 613 – FDA end-of-Phase 2 meeting; Phase 3 design in H2:21
Milestones EB 612 – Formulation for Phase 2b/Phase 3 in 2021
EB 613 – Phase 3 commencement of patient enrollment expected in 2022
& Highlights
Potential Business Development Collaborations:
Lead program commercial rights and new proprietary compounds, similar to Amgen
Strong Balance Sheet: >$28 M of Cash on August 8th 2021; Cash runway through
end of Q4 2022
~28 M shares O/S (primary); ~31 M shares (FD)
Experienced management team & board
20 NASDAQ: ENTX 20You can also read
